Stimuli-responsive nano material and application thereof in preparation of in-situ tumor vaccine
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A technology of stimuli response and nanomaterials, applied in the direction of nanotechnology, nanotechnology, nanomedicine, etc., can solve the problems of genetic material changes, inability to effectively activate immune response, protein denaturation, etc., to enhance DC cell phagocytosis and enhance T cell Recruitment, effect of efficiency improvement
Pending Publication Date: 2022-02-18
DONGFANG HOSPITAL BEIJING UNIV OF CHINESE MEDICINE +1
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Although the tumor fragments produced in the tumor area after cryoablation cannot effectively activate the immune response due to the immunosuppressive environment in the tumor area and the insufficient activation of antigen-presenting cells, the antigenic information retained by these tumor fragments will not be changed because freezing will not change the biological characteristics. More complete, promising nano-tumor vaccines, providing more immunogenic fragments of antigens
Other tumor physical therapies such as radiotherapy, photothermal, radiofrequency ablation, and photodynamics can cause changes in the properties of tumor fragments. For example, photothermal and radiofrequency ablation can cause protein denaturation, and radiotherapy and photodynamic therapy can cause genetic material changes.
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Embodiment 1
[0070] Example 1: Temperature and pH stimulus-responsive nanomaterial APNPs and its preparation
[0071] This embodiment is a method for preparing temperature and pH stimulus-responsive nanomaterials, which specifically includes the following steps:
[0072] (1) Preparation of stimuli-responsive polymer carrier
[0073] Pluronic F127 (300mgmL) activated by 4-nitrophenyl chloroformate (4-NPC) -1 , 500mL) was dissolved in dichloromethane, under ultrasonic treatment (30% ultrasonic power, 3 minutes), was added dropwise to chitosan aqueous solution (15mgmL -1 , 5 mL, pH=10), after removing dichloromethane by rotary evaporation, the resulting solution was dialyzed overnight in deionized water with a dialysis tube (50 kDa), and then dialyzed in deionized water with a (1000 kDa) dialysis tube for 3 hours, Freeze-drying the prepared stimulus-responsive polymer carrier for further use;
[0074] (2) Surface functional modification of stimuli-responsive polymer carriers
[0075] Add ...
Embodiment 2
[0080] Example 2: Temperature and pH stimulus-responsive nanomaterials PNPs and their preparation
[0081] The preparation steps of APNPs in Example 1 were the same, except that astragalus polysaccharide (APS) was not added during encapsulation, so that temperature and pH stimulus-responsive nanomaterial PNPs were obtained.
Embodiment 3
[0082] Example 3: Other temperature and pH stimulus-responsive nanomaterials and their preparation
[0083] The difference between this embodiment and Example 1 is that the dichloromethane in the step (1) of Example 1 is replaced by other organic solvents such as styrene, perchlorethylene, trichloroethylene, ethylene glycol ether and triethanolamine Wait.
[0084] In this example, a temperature- and pH-stimulus-responsive nanomaterial for encapsulating astragalus polysaccharide and polyinosinic acid-polycytidylic acid was prepared.
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Abstract
The invention relates to a stimuli-responsive nano material, which can be combined with an antigen generated by cryoablation to form a nano in-situ tumor vaccine, can realize the functions of lymph node targeting, in-vivo tumor fragment adsorption, targeted activation of antigen-presenting cells, pH-responsive drug controlled release, drug loading and the like, and provides a new method and a new technology for tumor immunotherapy. On the one hand, tumor fragments generated by cryoablation retain more antigen information, and an antigen presentation system can be activated more efficiently; and on the other hand, the stimuli-responsive nano material effectively adsorbs tumor fragments and can carry a pattern recognition receptor stimulant or drug, so that the ability of targeting and activating antigen-presenting cells is enhanced. According to the stimuli-responsive nano in-situ tumor vaccine prepared by the invention, tumor antigens generated by cryoablation are loaded, so that the defect that the cryoablation cannot kill far-end focuses and free tumor cells is overcome, and the stimuli-responsive nano in-situ tumor vaccine is expected to induce systemic immunotherapy while killing local focuses.
Description
technical field [0001] The disclosure belongs to the field of macromolecular materials, and in particular relates to a stimulus-responsive nanometer material and antigens produced by cryoablation to form nanometer in situ tumor vaccines, including related preparation methods and applications. Background technique [0002] In recent years, the development of tumor treatment methods represented by surgical resection, radiotherapy and chemotherapy has fallen into a bottleneck, while immunotherapy, as an emerging treatment mode, has shown higher application prospects in the treatment of various tumors. At present, tumor immunotherapy is mainly divided into two types: active immunotherapy and passive immunotherapy. Compared with passive immunization represented by CAR-T, antibody and cytokine therapy, active immunization represented by tumor vaccines is not only effective in many tumors. The curative effect is better, and it also has the advantages of long-term immunity and low a...
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